LIVIVO - Search results -

Search results

Result 1 - 10 of total 12

Search options

Article ; Online: A method to specifically activate the Klotho promoter by using zinc finger proteins constructed from modular building blocks and from naturally engineered Egr1 transcription factor backbone.

Chen, Ci-Di / Rudy, Melissa A / Zeldich, Ella / Abraham, Carmela R

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2020 Volume 34, Issue 6, Page(s) 7234–7246

Abstract: There is an unmet need for treatments for diseases associated with aging. The antiaging, life-extending, and cognition-enhancing protein Klotho is neuroprotective due to its anti-inflammatory, antioxidative, and pro-myelinating effects. In addition, ... ...

Abstract	There is an unmet need for treatments for diseases associated with aging. The antiaging, life-extending, and cognition-enhancing protein Klotho is neuroprotective due to its anti-inflammatory, antioxidative, and pro-myelinating effects. In addition, Klotho is also a tumor suppressor and has beneficial roles in multiple organs. Klotho is downregulated as part of the aging process. Thus, upregulating Klotho in the brain may lead to novel therapeutics to people suffering or at risk for neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis, and demyelinating diseases such as multiple sclerosis. We attempted to upregulate Klotho for its beneficial effects in the brain and elsewhere. Here, we describe a method to specifically activate Klotho gene expression. To accomplish this task, we designed zinc finger proteins (ZFPs) targeting within -300 bps of the human Klotho promoter. We designed the ZPF constructs either de novo from modular building blocks, or modified sequences from the natural endogenous Egr1 transcription factor backbone structure. Egr1 is known to upregulate Klotho expression. We tested the transcriptional activation effects of these ZFPs in a dual luciferase coincidence reporter system under the control of 4-kb promoter of human Klotho in stable HEK293 cells and in HK-2 cells that express Klotho protein endogenously. We found that the best ZFPs are the de novo designed ones targeting -250 bps of Klotho promoter and one of the Egr1-binding sites. We further enhanced Klotho's activation using p65-Rta transcriptional activation domains in addition to VP64. These upregulation approaches could be useful for studying Klotho's protective effects and designing Klotho boosting therapeutics for future in vivo experiments.
MeSH term(s)	Aging/genetics ; Binding Sites/genetics ; Brain/metabolism ; Cell Line ; Cognition/physiology ; Early Growth Response Protein 1/genetics ; Gene Expression/genetics ; Glucuronidase/genetics ; HEK293 Cells ; Humans ; Luciferases/genetics ; Neurodegenerative Diseases/genetics ; Neurodegenerative Diseases/metabolism ; Promoter Regions, Genetic/genetics ; Transcriptional Activation/genetics ; Up-Regulation/genetics ; Zinc Fingers/genetics
Chemical Substances	EGR1 protein, human ; Early Growth Response Protein 1 ; Luciferases (EC 1.13.12.-) ; Glucuronidase (EC 3.2.1.31) ; klotho protein (EC 3.2.1.31)
Language	English
Publishing date	2020-04-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.202000171R
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2266: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 296: Show issues

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾

Article: Coordinated stimulation of axon regenerative and neurodegenerative transcriptional programs by Atf4 following optic nerve injury.

Somasundaram, Preethi / Farley, Madeline M / Rudy, Melissa A / Stefanoff, David G / Shah, Malay / Goli, Puneetha / Heo, Jenny / Wang, Shufang / Tran, Nicholas M / Watkins, Trent A

bioRxiv : the preprint server for biology

2023

Abstract: Previously we showed that neurodegeneration initiated by axonal insults depends in part on the stress-responsive kinase Perk (Larhammar et al., 2017). Here we show that Perk acts primarily through Activating Transcription Factor-4 (Atf4) to stimulate not ...

Abstract	Previously we showed that neurodegeneration initiated by axonal insults depends in part on the stress-responsive kinase Perk (Larhammar et al., 2017). Here we show that Perk acts primarily through Activating Transcription Factor-4 (Atf4) to stimulate not only pro-apoptotic but also pro-regenerative responses following optic nerve injury. Using conditional knockout mice, we find an extensive Perk/Atf4-dependent transcriptional response that includes canonical Atf4 target genes and modest contributions by C/ebp homologous protein (Chop). Overlap with c-Jun-dependent transcription suggests interplay with a parallel stress pathway that couples regenerative and apoptotic responses. Accordingly, neuronal knockout of Atf4 recapitulates the neuroprotection afforded by Perk deficiency, and Perk or Atf4 knockout impairs optic axon regeneration enabled by disrupting the tumor suppressor Pten. These findings contrast with the transcriptional and functional consequences reported for CRISPR targeting of Atf4 or Chop and reveal an integral role for Perk/Atf4 in coordinating neurodegenerative and regenerative responses to CNS axon injury.
Language	English
Publishing date	2023-03-31
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.29.534798
Database	MEDical Literature Analysis and Retrieval System OnLINE

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

Article ; Online: High-depth sequencing characterization of viral dynamics across tissues in fatal COVID-19 reveals compartmentalized infection.

Normandin, Erica / Rudy, Melissa / Barkas, Nikolaos / Schaffner, Stephen F / Levine, Zoe / Padera, Robert F / Babadi, Mehrtash / Mukerji, Shibani S / Park, Daniel J / MacInnis, Bronwyn L / Siddle, Katherine J / Sabeti, Pardis C / Solomon, Isaac H

Nature communications

2023 Volume 14, Issue 1, Page(s) 574

Abstract: SARS-CoV-2 distribution and circulation dynamics are not well understood due to challenges in assessing genomic data from tissue samples. We develop experimental and computational workflows for high-depth viral sequencing and high-resolution genomic ... ...

Abstract	SARS-CoV-2 distribution and circulation dynamics are not well understood due to challenges in assessing genomic data from tissue samples. We develop experimental and computational workflows for high-depth viral sequencing and high-resolution genomic analyses from formalin-fixed, paraffin-embedded tissues and apply them to 120 specimens from six subjects with fatal COVID-19. To varying degrees, viral RNA is present in extrapulmonary tissues from all subjects. The majority of the 180 viral variants identified within subjects are unique to individual tissue samples. We find more high-frequency (>10%) minor variants in subjects with a longer disease course, with one subject harboring ten such variants, exclusively in extrapulmonary tissues. One tissue-specific high-frequency variant was a nonsynonymous mutation in the furin-cleavage site of the spike protein. Our findings suggest adaptation and/or compartmentalized infection, illuminating the basis of extrapulmonary COVID-19 symptoms and potential for viral reservoirs, and have broad utility for investigating human pathogens.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2/genetics ; SARS-CoV-2/metabolism ; Mutation ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism
Chemical Substances	Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2023-02-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-34256-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Identification of the cleavage sites leading to the shed forms of human and mouse anti-aging and cognition-enhancing protein Klotho.

Chen, Ci-Di / Li, Yuexuan / Chen, Arthur K / Rudy, Melissa A / Nasse, Jason S / Zeldich, Ella / Polanco, Taryn J / Abraham, Carmela R

PloS one

2020 Volume 15, Issue 1, Page(s) e0226382

Abstract: Klotho is an age-extending, cognition-enhancing protein found to be down-regulated in aged mammals when age-related diseases start to appear. Low levels of Klotho occur in neurodegenerative diseases, kidney disease and many cancers. Many normal and ... ...

Abstract	Klotho is an age-extending, cognition-enhancing protein found to be down-regulated in aged mammals when age-related diseases start to appear. Low levels of Klotho occur in neurodegenerative diseases, kidney disease and many cancers. Many normal and pathologic processes involve the proteolytic shedding of membrane proteins. Transmembrane (TM) Klotho contains two homologous domains, KL1 and KL2 with homology to glycosidases. After shedding by ADAM 10 and 17, a shed Klotho isoform is released into serum and urine by the kidney, and into the CSF by the choroid plexus. We previously reported that human Klotho contains two major cleavage sites. However, the exact cleavage site responsible for the cleavage between the KL1 and KL2 domains remains unknown for the human Klotho, and both sites are unknown for mouse Klotho. In this study, we aimed to identify the cleavage sites leading to the shed forms of human and mouse Klotho. Mutations in the region close to the TM domain of mouse Klotho result in the reduced shedding of the 130 kD (KL1+KL2) and 70 kD (KL1) fragments, suggesting that the cleavage site lies within the mutated region. We further identified the cleavage sites responsible for the cleavage between KL1 and KL2 of human and mouse Klotho. Moreover, mutated Klotho proteins have similar subcellular localization patterns as wild type Klotho. Finally, in an FGF23 functional assay, all Klotho mutants with a nine amino acid deletion can also function as an FGFR1 co-receptor for FGF23 signaling, however, the signaling activity was greatly reduced. The study provides new and important information on Klotho shedding, and paves the way for studies aimed to distinguish between the distinct roles of the various isoforms of Klotho.
MeSH term(s)	ADAM10 Protein/metabolism ; Amino Acid Sequence ; Animals ; COS Cells ; Chlorocebus aethiops ; Fibroblast Growth Factors/metabolism ; Glucuronidase/chemistry ; Glucuronidase/genetics ; Glucuronidase/metabolism ; HEK293 Cells ; Humans ; Mice ; Microscopy, Fluorescence ; Mutagenesis ; Protein Domains ; Protein Isoforms/chemistry ; Protein Isoforms/genetics ; Protein Isoforms/metabolism ; Receptor, Fibroblast Growth Factor, Type 1/metabolism ; Sequence Alignment ; Signal Transduction
Chemical Substances	Protein Isoforms ; Fibroblast Growth Factors (62031-54-3) ; fibroblast growth factor 23 (7Q7P4S7RRE) ; Receptor, Fibroblast Growth Factor, Type 1 (EC 2.7.10.1) ; Glucuronidase (EC 3.2.1.31) ; klotho protein (EC 3.2.1.31) ; ADAM10 Protein (EC 3.4.24.81)
Language	English
Publishing date	2020-01-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0226382
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Natural history of Ebola virus disease in rhesus monkeys shows viral variant emergence dynamics and tissue-specific host responses.

Normandin, Erica / Triana, Sergio / Raju, Siddharth S / Lan, Tammy C T / Lagerborg, Kim / Rudy, Melissa / Adams, Gordon C / DeRuff, Katherine C / Logue, James / Liu, David / Strebinger, Daniel / Rao, Arya / Messer, Katelyn S / Sacks, Molly / Adams, Ricky D / Janosko, Krisztina / Kotliar, Dylan / Shah, Rickey / Crozier, Ian /

Rinn, John L / Melé, Marta / Honko, Anna N / Zhang, Feng / Babadi, Mehrtash / Luban, Jeremy / Bennett, Richard S / Shalek, Alex K / Barkas, Nikolaos / Lin, Aaron E / Hensley, Lisa E / Sabeti, Pardis C / Siddle, Katherine J

Cell genomics

2023 Volume 3, Issue 12, Page(s) 100440

Abstract: Ebola virus (EBOV) causes Ebola virus disease (EVD), marked by severe hemorrhagic fever; however, the mechanisms underlying the disease remain unclear. To assess the molecular basis of EVD across time, we performed RNA sequencing on 17 tissues from a ... ...

Abstract	Ebola virus (EBOV) causes Ebola virus disease (EVD), marked by severe hemorrhagic fever; however, the mechanisms underlying the disease remain unclear. To assess the molecular basis of EVD across time, we performed RNA sequencing on 17 tissues from a natural history study of 21 rhesus monkeys, developing new methods to characterize host-pathogen dynamics. We identified alterations in host gene expression with previously unknown tissue-specific changes, including downregulation of genes related to tissue connectivity. EBOV was widely disseminated throughout the body; using a new, broadly applicable deconvolution method, we found that viral load correlated with increased monocyte presence. Patterns of viral variation between tissues differentiated primary infections from compartmentalized infections, and several variants impacted viral fitness in a EBOV/Kikwit minigenome system, suggesting that functionally significant variants can emerge during early infection. This comprehensive portrait of host-pathogen dynamics in EVD illuminates new features of pathogenesis and establishes resources to study other emerging pathogens.
MeSH term(s)	Animals ; Hemorrhagic Fever, Ebola/pathology ; Macaca mulatta ; Ebolavirus/genetics ; Hemorrhagic Fevers, Viral
Language	English
Publishing date	2023-11-21
Publishing country	United States
Document type	Journal Article
ISSN	2666-979X
ISSN (online)	2666-979X
DOI	10.1016/j.xgen.2023.100440
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Intrathecal inflammatory responses in the absence of SARS-CoV-2 nucleic acid in the CSF of COVID-19 hospitalized patients.

Journal of the neurological sciences

2021 Volume 430, Page(s) 120023

Abstract: Objective: Little is known about CSF profiles in patients with acute COVID-19 infection and neurological symptoms. Here, CSF was tested for SARS-CoV-2 RNA and inflammatory cytokines and chemokines and compared to controls and patients with known ... ...

Abstract	Objective: Little is known about CSF profiles in patients with acute COVID-19 infection and neurological symptoms. Here, CSF was tested for SARS-CoV-2 RNA and inflammatory cytokines and chemokines and compared to controls and patients with known neurotropic pathogens. Methods: CSF from twenty-seven consecutive patients with COVID-19 and neurological symptoms was assayed for SARS-CoV-2 RNA using quantitative reverse transcription PCR (RT-qPCR) and unbiased metagenomic sequencing. Assays for blood brain barrier (BBB) breakdown (CSF:serum albumin ratio (Q-Alb)), and proinflammatory cytokines and chemokines (IL-6, IL-8, IL-15, IL-16, monocyte chemoattractant protein -1 (MCP-1) and monocyte inhibitory protein - 1β (MIP-1β)) were performed in 23 patients and compared to CSF from patients with HIV-1 (16 virally suppressed, 5 unsuppressed), West Nile virus (WNV) (n = 4) and 16 healthy controls (HC). Results: Median CSF cell count for COVID-19 patients was 1 white blood cell/μL; two patients were infected with a second pathogen (Neisseria, Cryptococcus neoformans). No CSF samples had detectable SARS-CoV-2 RNA by either detection method. In patients with COVID-19 only, CSF IL-6, IL-8, IL-15, and MIP-1β levels were higher than HC and suppressed HIV (corrected-p < 0.05). MCP-1 and MIP-1β levels were higher, while IL-6, IL-8, IL-15 were similar in COVID-19 compared to WNV patients. Q-Alb correlated with all proinflammatory markers, with IL-6, IL-8, and MIP-1β (r ≥ 0.6, p < 0.01) demonstrating the strongest associations. Conclusions: Lack of SARS-CoV-2 RNA in CSF is consistent with pre-existing literature. Evidence of intrathecal proinflammatory markers in a subset of COVID-19 patients with BBB breakdown despite minimal CSF pleocytosis is atypical for neurotropic pathogens.
MeSH term(s)	Blood-Brain Barrier ; COVID-19/physiopathology ; Case-Control Studies ; Chemokines ; Cytokines ; Humans ; Inflammation/virology ; RNA, Viral/cerebrospinal fluid ; SARS-CoV-2
Chemical Substances	Chemokines ; Cytokines ; RNA, Viral
Language	English
Publishing date	2021-10-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	80160-4
ISSN	1878-5883 ; 0022-510X ; 0374-8642
ISSN (online)	1878-5883
ISSN	0022-510X ; 0374-8642
DOI	10.1016/j.jns.2021.120023
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 308: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Phylogenetic analysis of SARS-CoV-2 in the Boston area highlights the role of recurrent importation and superspreading events.

Lemieux, Jacob E / Siddle, Katherine J / Shaw, Bennett M / Loreth, Christine / Schaffner, Stephen F / Gladden-Young, Adrianne / Adams, Gordon / Fink, Timelia / Tomkins-Tinch, Christopher H / Krasilnikova, Lydia A / DeRuff, Katherine C / Rudy, Melissa / Bauer, Matthew R / Lagerborg, Kim A / Normandin, Erica / Chapman, Sinead B / Reilly, Steven K / Anahtar, Melis N / Lin, Aaron E /

Carter, Amber / Myhrvold, Cameron / Kemball, Molly E / Chaluvadi, Sushma / Cusick, Caroline / Flowers, Katelyn / Neumann, Anna / Cerrato, Felecia / Farhat, Maha / Slater, Damien / Harris, Jason B / Branda, John / Hooper, David / Gaeta, Jessie M / Baggett, Travis P / O'Connell, James / Gnirke, Andreas / Lieberman, Tami D / Philippakis, Anthony / Burns, Meagan / Brown, Catherine M / Luban, Jeremy / Ryan, Edward T / Turbett, Sarah E / LaRocque, Regina C / Hanage, William P / Gallagher, Glen R / Madoff, Lawrence C / Smole, Sandra / Pierce, Virginia M / Rosenberg, Eric / Sabeti, Pardis C / Park, Daniel J / Maclnnis, Bronwyn L

medRxiv : the preprint server for health sciences

2020

Abstract: SARS-CoV-2 has caused a severe, ongoing outbreak of COVID-19 in Massachusetts with 111,070 confirmed cases and 8,433 deaths as of August 1, 2020. To investigate the introduction, spread, and epidemiology of COVID-19 in the Boston area, we sequenced and ... ...

Abstract	SARS-CoV-2 has caused a severe, ongoing outbreak of COVID-19 in Massachusetts with 111,070 confirmed cases and 8,433 deaths as of August 1, 2020. To investigate the introduction, spread, and epidemiology of COVID-19 in the Boston area, we sequenced and analyzed 772 complete SARS-CoV-2 genomes from the region, including nearly all confirmed cases within the first week of the epidemic and hundreds of cases from major outbreaks at a conference, a nursing facility, and among homeless shelter guests and staff. The data reveal over 80 introductions into the Boston area, predominantly from elsewhere in the United States and Europe. We studied two superspreading events covered by the data, events that led to very different outcomes because of the timing and populations involved. One produced rapid spread in a vulnerable population but little onward transmission, while the other was a major contributor to sustained community transmission, including outbreaks in homeless populations, and was exported to several other domestic and international sites. The same two events differed significantly in the number of new mutations seen, raising the possibility that SARS-CoV-2 superspreading might encompass disparate transmission dynamics. Our results highlight the failure of measures to prevent importation into MA early in the outbreak, underscore the role of superspreading in amplifying an outbreak in a major urban area, and lay a foundation for contact tracing informed by genetic data.
Keywords	covid19
Language	English
Publishing date	2020-08-25
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.08.23.20178236
Database	MEDical Literature Analysis and Retrieval System OnLINE

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

Article ; Online: Phylogenetic analysis of SARS-CoV-2 in Boston highlights the impact of superspreading events.

Lemieux, Jacob E / Siddle, Katherine J / Shaw, Bennett M / Loreth, Christine / Schaffner, Stephen F / Gladden-Young, Adrianne / Adams, Gordon / Fink, Timelia / Tomkins-Tinch, Christopher H / Krasilnikova, Lydia A / DeRuff, Katherine C / Rudy, Melissa / Bauer, Matthew R / Lagerborg, Kim A / Normandin, Erica / Chapman, Sinéad B / Reilly, Steven K / Anahtar, Melis N / Lin, Aaron E /

Carter, Amber / Myhrvold, Cameron / Kemball, Molly E / Chaluvadi, Sushma / Cusick, Caroline / Flowers, Katelyn / Neumann, Anna / Cerrato, Felecia / Farhat, Maha / Slater, Damien / Harris, Jason B / Branda, John A / Hooper, David / Gaeta, Jessie M / Baggett, Travis P / O'Connell, James / Gnirke, Andreas / Lieberman, Tami D / Philippakis, Anthony / Burns, Meagan / Brown, Catherine M / Luban, Jeremy / Ryan, Edward T / Turbett, Sarah E / LaRocque, Regina C / Hanage, William P / Gallagher, Glen R / Madoff, Lawrence C / Smole, Sandra / Pierce, Virginia M / Rosenberg, Eric / Sabeti, Pardis C / Park, Daniel J / MacInnis, Bronwyn L

Science (New York, N.Y.)

2020 Volume 371, Issue 6529

Abstract: Analysis of 772 complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from early in the Boston-area epidemic revealed numerous introductions of the virus, a small number of which led to most cases. The data revealed two ... ...

Abstract	Analysis of 772 complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from early in the Boston-area epidemic revealed numerous introductions of the virus, a small number of which led to most cases. The data revealed two superspreading events. One, in a skilled nursing facility, led to rapid transmission and significant mortality in this vulnerable population but little broader spread, whereas other introductions into the facility had little effect. The second, at an international business conference, produced sustained community transmission and was exported, resulting in extensive regional, national, and international spread. The two events also differed substantially in the genetic variation they generated, suggesting varying transmission dynamics in superspreading events. Our results show how genomic epidemiology can help to understand the link between individual clusters and wider community spread.
MeSH term(s)	Boston/epidemiology ; COVID-19/epidemiology ; COVID-19/transmission ; Disease Outbreaks ; Epidemiological Monitoring ; Genome, Viral ; Humans ; Phylogeny ; SARS-CoV-2/genetics
Language	English
Publishing date	2020-12-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.abe3261
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 27: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 77: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Phylogenetic analysis of SARS-CoV-2 in the Boston area highlights the role of recurrent importation and superspreading events

Lemieux, Jacob / Siddle, Katherine J / Shaw, Bennett M. / Loreth, Christine / Schaffner, Stephen / Gladden-Young, Adrianne / Adams, Gordon / Fink, Timelia / Tomkins-Tinch, Chris H / Krasilnikova, Lydia A / Deruff, Katherine C / Rudy, Melissa / Bauer, Matthew R / Lagerborg, Kim A / Normandin, Erica / Chapman, Sinead B / Reilly, Steven K / Anahtar, Melis N / Lin, Aaron E /

Carter, Amber / Myhrvold, Cameron / Kemball, Molly / Chaluvadi, Suschma / Cusick, Caroline / Flowers, Katelyn / Neumann, Anna / Cerrato, Felecia / Farhat, Maha / Slater, Damien / Harris, Jason B / Branda, John / Hooper, David / Gaeta, Jessie M / Baggett, Travis P. / O'Connell, James / Gnirke, Andreas / Lieberman, Tami D / Philippakis, Anthony / Burns, Meagan / Brown, Catherine / Luban, Jeremy / Ryan, Edward T / Turbett, Sarah E / LaRocque, Regina C / Hanage, William P. / Gallagher, Glen / Madoff, Lawrence C / Smole, Sandra / Pierce, Virginia M. / Rosenberg, Eric S / Sabeti, Pardis / Park, Daniel J / MacInnis, Bronwyn L

medRxiv

Abstract	SARS-CoV-2 has caused a severe, ongoing outbreak of COVID-19 in Massachusetts with 111,070 confirmed cases and 8,433 deaths as of August 1, 2020. To investigate the introduction, spread, and epidemiology of COVID-19 in the Boston area, we sequenced and analyzed 772 complete SARS-CoV-2 genomes from the region, including nearly all confirmed cases within the first week of the epidemic and hundreds of cases from major outbreaks at a conference, a nursing facility, and among homeless shelter guests and staff. The data reveal over 80 introductions into the Boston area, predominantly from elsewhere in the United States and Europe. We studied two superspreading events covered by the data, events that led to very different outcomes because of the timing and populations involved. One produced rapid spread in a vulnerable population but little onward transmission, while the other was a major contributor to sustained community transmission, including outbreaks in homeless populations, and was exported to several other domestic and international sites. The same two events differed significantly in the number of new mutations seen, raising the possibility that SARS-CoV-2 superspreading might encompass disparate transmission dynamics. Our results highlight the failure of measures to prevent importation into MA early in the outbreak, underscore the role of superspreading in amplifying an outbreak in a major urban area, and lay a foundation for contact tracing informed by genetic data.
Keywords	covid19
Language	English
Publishing date	2020-08-25
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2020.08.23.20178236
Database	COVID19

Full text online

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: A single-cell and spatial atlas of autopsy tissues reveals pathology and cellular targets of SARS-CoV-2.

Delorey, Toni M / Ziegler, Carly G K / Heimberg, Graham / Normand, Rachelly / Yang, Yiming / Segerstolpe, Asa / Abbondanza, Domenic / Fleming, Stephen J / Subramanian, Ayshwarya / Montoro, Daniel T / Jagadeesh, Karthik A / Dey, Kushal K / Sen, Pritha / Slyper, Michal / Pita-Juárez, Yered H / Phillips, Devan / Bloom-Ackerman, Zohar / Barkas, Nick / Ganna, Andrea /

Gomez, James / Normandin, Erica / Naderi, Pourya / Popov, Yury V / Raju, Siddharth S / Niezen, Sebastian / Tsai, Linus T-Y / Siddle, Katherine J / Sud, Malika / Tran, Victoria M / Vellarikkal, Shamsudheen K / Amir-Zilberstein, Liat / Atri, Deepak S / Beechem, Joseph / Brook, Olga R / Chen, Jonathan / Divakar, Prajan / Dorceus, Phylicia / Engreitz, Jesse M / Essene, Adam / Fitzgerald, Donna M / Fropf, Robin / Gazal, Steven / Gould, Joshua / Grzyb, John / Harvey, Tyler / Hecht, Jonathan / Hether, Tyler / Jane-Valbuena, Judit / Leney-Greene, Michael / Ma, Hui / McCabe, Cristin / McLoughlin, Daniel E / Miller, Eric M / Muus, Christoph / Niemi, Mari / Padera, Robert / Pan, Liuliu / Pant, Deepti / Pe'er, Carmel / Pfiffner-Borges, Jenna / Pinto, Christopher J / Plaisted, Jacob / Reeves, Jason / Ross, Marty / Rudy, Melissa / Rueckert, Erroll H / Siciliano, Michelle / Sturm, Alexander / Todres, Ellen / Waghray, Avinash / Warren, Sarah / Zhang, Shuting / Zollinger, Daniel R / Cosimi, Lisa / Gupta, Rajat M / Hacohen, Nir / Hide, Winston / Price, Alkes L / Rajagopal, Jayaraj / Tata, Purushothama Rao / Riedel, Stefan / Szabo, Gyongyi / Tickle, Timothy L / Hung, Deborah / Sabeti, Pardis C / Novak, Richard / Rogers, Robert / Ingber, Donald E / Jiang, Z Gordon / Juric, Dejan / Babadi, Mehrtash / Farhi, Samouil L / Stone, James R / Vlachos, Ioannis S / Solomon, Isaac H / Ashenberg, Orr / Porter, Caroline B M / Li, Bo / Shalek, Alex K / Villani, Alexandra-Chloé / Rozenblatt-Rosen, Orit / Regev, Aviv

bioRxiv : the preprint server for biology

2021

Abstract: The SARS-CoV-2 pandemic has caused over 1 million deaths globally, mostly due to acute lung injury and acute respiratory distress syndrome, or direct complications resulting in multiple-organ failures. Little is known about the host tissue immune and ... ...

Abstract	The SARS-CoV-2 pandemic has caused over 1 million deaths globally, mostly due to acute lung injury and acute respiratory distress syndrome, or direct complications resulting in multiple-organ failures. Little is known about the host tissue immune and cellular responses associated with COVID-19 infection, symptoms, and lethality. To address this, we collected tissues from 11 organs during the clinical autopsy of 17 individuals who succumbed to COVID-19, resulting in a tissue bank of approximately 420 specimens. We generated comprehensive cellular maps capturing COVID-19 biology related to patients' demise through single-cell and single-nucleus RNA-Seq of lung, kidney, liver and heart tissues, and further contextualized our findings through spatial RNA profiling of distinct lung regions. We developed a computational framework that incorporates removal of ambient RNA and automated cell type annotation to facilitate comparison with other healthy and diseased tissue atlases. In the lung, we uncovered significantly altered transcriptional programs within the epithelial, immune, and stromal compartments and cell intrinsic changes in multiple cell types relative to lung tissue from healthy controls. We observed evidence of: alveolar type 2 (AT2) differentiation replacing depleted alveolar type 1 (AT1) lung epithelial cells, as previously seen in fibrosis; a concomitant increase in myofibroblasts reflective of defective tissue repair; and, putative TP63
Language	English
Publishing date	2021-02-25
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.02.25.430130
Database	MEDical Literature Analysis and Retrieval System OnLINE

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

To top

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Inter-library loan at ZB MED